(23R,231 S,25S)-231,26-Epoxy-23-ethylfurost-20(22)-en-3β-ol

The title steroid includes a tetrahydro-2H-pyran heterocycle bonded to the steroidal nucleus, resulting from a spirostan rearrangement.

The title compound, C 29 H 46 O 3 , is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring F is a tetrahydro-2H-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while dihydrofuran ring E, to which it is bonded, has an envelope conformation. The molecules are associated by weak O-HÁ Á ÁO hydrogen bonds to form chains running in the [101] direction in the crystal.

Structure description
The title steroid (2) was synthesized, starting from a derivative of sarsasapogenin (1), through a cleavage of ring F in acidic medium, followed by a Michael-type nucleophilic attack that affords a tetrahydro-2H-pyran ring bonded to the steroidal E ring (Fig. 1). The crystal structure of 1Á0.5H 2 O has been reported previously (Viñ as-Bravo et al., 2003). On the other hand, the mechanism for the rearrangement 1!2 was described previously using a diosgenin derivative as substrate, instead of sarsasapogenin (del Río et al., 2006). As expected from this mechanism, both methyl groups substituting the pyran ring in 2 are placed in equatorial positions, defining the stereochemistry for atoms C25 and C27 as S,S (Fig. 2). The pyran ring adopts a chair conformation, characterized by a puckering amplitude q = 0.578 (4) Å . Surprisingly, the Cambridge Structural Database (Version 5.43, with all updates;Groom et al., 2016) does not contain any structure including the same heterocycle. However, many polysubstituted monocyclic tetrahydro-2H-pyran structures have been characterized by X-ray diffraction, showing that the chair confor-data reports mation is almost always stabilized (e.g. Burton et al., 2007). Only a few exceptions to this rule are known, for some large molecules with steric hindrance issues (e.g. Aydillo et al., 2013).
The 2,3-dihydrofuran ring E in 2 is close to being planar due to the presence of the C20 C22 double bond [1.324 (5) Å ], also evidenced by a vibration at 1627 cm À1 in the IR spectrum. The conformation can be described as an envelope with atom C16 as the flap, which belongs to the C-C bond fusing the D and E rings. The E ring has a small puckering amplitude, q = 0.184 (4) Å . A very similar conformation was observed in other steroids having the same E ring (Shen et al., 2013;Jeong & Fuchs, 1994). The remainder of the molecular structure, i.e. the A/B/C/D steroidal nucleus, is identical to that of sarsasapogenin, with cis-fused A/B rings.
The crystal structure is very simple, since it is based on a single weak O-HÁ Á ÁO hydrogen bond, involving the hydroxy group at C3 and the O-atom acceptor of the tetrahydro-2Hpyran ring, O26 (Table 1 and  The molecular structure of 2 is embedded in a broader project aimed at targeting steroidal compounds which could interact with signalling pathways that control skeletal muscle atrophy and hypertrophy (Cohen et al., 2015). Indeed, the web tool SwissTargetPrediction (Daina et al., 2019) predicts that compound 2 presents a binding affinity for androgen and estrogen receptors, as well as for PI3K enzyme.

Synthesis and crystallization
In a round-bottomed flask was dissolved 275 mg (0.62 mmol) of 1 and 150 mg of pTsOH (ca 0.9 mmol) in 5 ml of benzene, and this mixture was refluxed for 30 min. The crude was then evaporated and the resulting solid dissolved in CH 2 Cl 2 , washed with distilled H 2 O, dried over Na 2 SO 4 and evaporated in vacuo to dryness. The residue was purified by chromato-   The synthesis of the title compound, 2, starting from 1. The atom-numbering scheme follows the recommendations of IUPAC (Moss, 1989). Key R/S configurations are displayed in red. pTsOH is p-toluenesulfonic acid.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were placed in calculated positions, with C-H = 1.00 (methine CH), 0.99 (methylene CH 2 ) or 0.98 Å (methyl CH 3 ). Atom H3A (of the hydroxy group) was refined with free coordinates. Isotropic displacement parameters for the H atoms were calculated as U iso (H) = xU eq (carrier atom), with x = 1.5 for methyl groups and the hydroxy H atom, and x = 1.2 for the other H atoms. The methyl groups were allowed to rotate but not to tip. Due to the absence of anomalous scatterers, the absolute configuration could not be determined and was set according to the starting material.

Funding information
Funding for this research was provided by: Consejo Nacional de Ciencia y Tecnología (grant Nos. 168178 and 171508).   (5)